U.S. patent application number 10/910988 was filed with the patent office on 2005-05-26 for quantitative biopolymer detecting system using monolithic piezoelectric cantilever by resonant frequency shift, method for fabricating the same system and method for detecting biopolymer quantitatively using the same system.
This patent application is currently assigned to Korea Institute of Science and Technology. Invention is credited to Hwang, Kyo Seon, Kim, Tae Song, Lee, Jeong Hoon, Park, Jae Bum.
Application Number | 20050112621 10/910988 |
Document ID | / |
Family ID | 34464743 |
Filed Date | 2005-05-26 |
United States Patent
Application |
20050112621 |
Kind Code |
A1 |
Kim, Tae Song ; et
al. |
May 26, 2005 |
Quantitative biopolymer detecting system using monolithic
piezoelectric cantilever by resonant frequency shift, method for
fabricating the same system and method for detecting biopolymer
quantitatively using the same system
Abstract
A method for detecting a small amount of biopolymer by using
resonant frequency shift of PZT monolithic cantilever system using
a cantilever includes: an infinitesimal fluid transfer system
having an inlet for allowing a reactant to be injected therethrough
and an infinitesimal introduction channel for connecting the inlet
and a reaction chamber; and a cantilever sensor installed in the
reaction chamber and having a cantilever with one end fixed at a
substrate, a piezoelectric capacitor for self-sensing and actuating
on at least one side of an upper surface and a lower surface of the
cantilever including a piezoelectric film, a lower electrode formed
at a lower surface of the piezoelectric film and an upper electrode
formed at an upper surface of the piezoelectric film, an electric
pad for applying electricity to the lower electrode and the upper
electrode, and a molecular recognition layer formed at least one
surface of the cantilever and so as to interact to an target
biopolymer.
Inventors: |
Kim, Tae Song; (Seoul,
KR) ; Hwang, Kyo Seon; (Icheon, KR) ; Park,
Jae Bum; (Seoul, KR) ; Lee, Jeong Hoon;
(Seoul, KR) |
Correspondence
Address: |
KUSNER & JAFFE
HIGHLAND PLACE SUITE 310
6151 WILSON MILLS ROAD
HIGHLAND HEIGHTS
OH
44143
US
|
Assignee: |
Korea Institute of Science and
Technology
|
Family ID: |
34464743 |
Appl. No.: |
10/910988 |
Filed: |
August 4, 2004 |
Current U.S.
Class: |
435/6.19 ;
435/4 |
Current CPC
Class: |
G01N 33/54373 20130101;
G01N 2291/0256 20130101; G01N 29/022 20130101; B01L 2300/0816
20130101; B01L 2300/0887 20130101; B01L 2300/0663 20130101; G01N
2291/0426 20130101; B82Y 30/00 20130101; B82Y 35/00 20130101; G01N
2291/0427 20130101; G01N 29/036 20130101; B01L 2400/0487 20130101;
G01N 29/4436 20130101; B01L 2300/0867 20130101 |
Class at
Publication: |
435/006 ;
435/004 |
International
Class: |
C12Q 001/00 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 25, 2003 |
KR |
84160/2003 |
Claims
Having described the invention, the following is claimed:
1. A method for detecting a small amount of biopolymer by using
resonant frequency shift of PZT monolithic cantilever system
comprising: an infinitesimal fluid transfer system including an
inlet for allowing a reactant to be injected therethrough, and an
infinitesimal introduction channel for connecting the inlet and a
reaction chamber; and a cantilever sensor including a cantilever
with one end fixed at a substrate, a piezoelectric thin film for
self-actuating and sensing deposited on at least one side of an
upper surface and a lower surface of the cantilever, a lower
electrode formed at a lower surface of the piezoelectric film and
an upper electrode formed at an upper surface of the piezoelectric
film, and an electric pad for supplying electricity to both the
lower electrode and the upper electrode, the cantilever sensor
being installed in the reaction chamber.
2. The system of claim 1 further comprising a molecular recognition
layer formed at least one surface of the cantilever so as to react
to a target biopolymer.
3. The system of claim 1, wherein the infinitesimal transfer system
has two or more inlets, and the inlet channel includes an entrance
channel with one end connected to the inlets and a mixing channel
with one end connected to a point where the inlet channels meet and
the other end connected to the reaction chamber.
4. The system of claim 3 further comprises a mixing chamber formed
at a point where the entrance channel and the mixing channel
meet.
5. The system of claim 1, wherein the infinitesimal fluid transfer
system further comprises: an outlet formed to allow a reactant to
be discharged; and an outlet channel connecting the outlet with the
reaction chamber.
6. The system of claim 5, wherein the outlet channel is connected
to an upper end of the reaction chamber.
7. The system of claim 1, wherein the inlet channel is connected to
a lower end of the reaction chamber.
8. The system of claim 1, wherein an optically transparent window
is formed to enable an optical measurement into the reaction
chamber from outside.
9. The system of claim 1, wherein the infinitesimal fluid transfer
system is made of a polymer material.
10. The system of claim 9, wherein the polymer material is
PDMS.
11. The system of claim 1, wherein the infinitesimal fluid transfer
system is made of a glass material.
12. The system of claim 11, wherein the glass material is made of
pyrex or quartz.
13. The system of claim 1, wherein an insulation film is formed to
cover the piezoelectric monolithic cantilever in order to prevent
conduction in a liquid.
14. The system of claim 13, wherein the insulation film is an
inorganic insulator.
15. The system of claim 14, wherein the inorganic insulator is
SiOx.
16. The system of claim 13, wherein the insulation film is an
organic insulator.
17. The system of claim 16, wherein the organic insulator is
parylene.
18. The system of claim 1 further comprising: an electric signal
pad connected to the upper electrode and the lower electrode and
detecting an electric signal.
19. The system of claim 1, wherein two or more cantilevers are
arrayed, and the self-actuating and sensing capacitor are formed at
every cantilever.
20. The system of claim 2, wherein two or more cantilevers are
arrayed, and the self-actuating and sensing capacitor, the
electrode pad and the molecular recognition layer are formed at
every cantilever.
21. The system of claim 1, wherein the piezoelectric capacitor is
formed on a single layer of silicon or silicon nitride film.
22. The system of claim 1, wherein the piezoelectric capacitor is
formed on a double layer of silicon nitride film and silicon.
23. The system of claim 1, wherein the piezoelectric capacitor is
formed on a double layer of silicon oxide layer and silicon.
24. The system of claim 1, wherein the piezoelectric capacitor is
formed on a triple layer of silicon oxide film, silicon nitride
film and silicon oxide film.
25. The system of claim 2, wherein the biopolymer receptor was
immobilized using a self assembled monolayers (SAMs) on cantilever
for the detection of target biopolymer.
26. The system of claim 25, wherein Cr and Au are deposited at a
surface of the cantilever, on which the SAM layer is formed.
27. A method for fabricating an element detecting system using a
cantilever, comprising: a step of forming a cantilever sensor
comprising fabricating a cantilever by using a MEMS technique,
forming a piezoelectric thin film for self-actuating and sensing
deposited on at least one side of an upper surface and a lower
surface of the cantilever, a lower electrode formed at a lower
surface of the piezoelectric film and an upper electrode formed at
an upper surface of the piezoelectric film, stacking an electronic
pad at certain portions of the upper electrode and the lower
electrode, and forming a molecular recognition layer at least one
side of the cantilever and the driving film; a step of forming
upper and lower molds to form an inlet, a reaction chamber and an
infinitesimal introduction channel for connecting the inlet and the
reaction chamber; a step of putting a dissolved mold material in
the molds and solidifying it to form upper and lower plates; a step
of fixing the cantilever sensor formed in the cantilever sensor
forming step in the reaction chamber; and a step of bonding the
upper and lower plates.
28. The method of claim 27, wherein the mold material is PDMS.
29. The method of claim 28, wherein the mold is formed on die
steel, Teflon or silicon.
30. The method of claim 27, wherein the mold material is glass.
31. The method of claim 27 further comprising: forming an
insulation film to cover the monolithic piezoelectric cantilever
after forming the electric pad.
32. A method for detecting a small amount of biopolymer by using
resonant frequency shift of PZT monolithic cantilever system using
a cantilever of claim 1 comprises: a step of injecting a cleaning
solution such as a PBS solution into the inlets to fill the
reaction chamber; a step of applying electricity to the electric
pads to obtain a reference resonant frequency of the cantilever; a
step of supplying an analysis solution toward the inlets and
maintaining the state so as for the analysis solution to react to
the molecular recognition layer; a step of injecting a cleaning
solution into the inlets to fill the chamber; a step of applying
electricity to the electric pads to obtain a resonant frequency of
the cantilever; and a step of comparing the reference resonant
frequency obtained in the second step with the resonant frequency
obtained in the fifth step.
33. The method of claim 32, wherein the cleaning solution is a PBS
solution.
34. In a method for detecting a micro material by using the element
detecting system using a cantilever of claim 1, an analysis
solution is injected into the inlet to fill the reaction chamber
and electricity is applied to the electric pad at every
predetermined time to thereby obtain a resonant frequency of the
cantilever.
35. A method for detecting a small amount of biopolymer by using
resonant frequency shift of PZT monolithic cantilever system using
a cantilever of claim 1 comprises: a step of injecting a cleaning
solution into the inlets to fill the chamber; a step of injecting
nitrogen gas into the inlets to remove the cleaning solution from
the chamber; a step of supplying electricity to the electric pads
to obtain a reference resonant frequency of the cantilever; a step
of supplying an analysis solution toward the inlets and maintaining
the state for a predetermined time so as for the analysis solution
to react to the molecular recognition layer; a step of injecting a
cleaning solution into the inlets to fill the chamber; a step of
injecting nitrogen gas into the inlets to remove the cleaning
solution from the chamber; a step of supplying electricity to the
electric pads to obtain a resonant frequency of the cantilever; and
a step of comparing the reference resonant frequency obtained in
the third step with the resonant frequency obtained in the seventh
step.
36. The method of claim 35, wherein the cleaning solution is
PBS.
37. A method for detecting a small amount of biopolymer by using
resonant frequency shift of PZT monolithic cantilever system using
a cantilever of claim 20, molecular recognition layers of each
cantilever are surface-processed differently in order to detect
several materials at one time.
38. In a method for measuring viscosity and density of a liquid by
using the element detecting system using a microcantilever of claim
1, a liquid is injected into a reaction chamber, and then, a
resonant frequency of the microcantilever and a change in the width
are measured to measure viscosity and density of a liquid.
39. The method of claim 38, wherein the liquid is blood plasma,
serum or blood, and decrease and increase of red blood cells is
detected by measuring viscosity and density of blood plasma, serum
or blood to thereby measure a degree of an illness.
40. In a method for sensing a material by using the element
detecting system using a microcantilever of claim 2, a reaction
material of the molecular recognition layer is in a gas state.
41. The method of claim 40, wherein the molecular recognition layer
is formed by solidifying gelatin, and the gas is humidity.
42. In a method for sensing biopolymer by using the element
detecting system using a microcantilever of claim 2, wherein the
molecular recognition layer includes an antibody reacting to
protein or DNA or complementary DNA, and the reaction material such
as protein or DNA is gasificated by lowering a pressure in a room
temperature, so as to react to the molecular recognition layer.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to an analyzing system for
sensing a small amount of protein and, more particularly, to an
analyzing system using a cantilever type sensor using resonant
frequency shift realizing reduced size thereof, sensing a protein
in a liquid as well as in the air, successively. In addition, the
present invention also relates to a sensing chip for sensing
various biopolymer such as DNA, protein, enzyme or a cell.
BACKGROUND OF THE INVENTION
[0002] A quartz crystal mass balance (QCM) is a conventional system
for sensing an analyte electrically or optically, which is,
however, not suitable for a mass production because a single quartz
crystal is too brittle to be formed small and thin.
[0003] Sensors using a cantilever under the researches measure a
static deflection to detect a change in a surface of the cantilever
(e.g. mass change thereof) caused by heat or gas adsorption to the
surface radiating a light source (e.g. laser).
[0004] The sensing method measuring static deflection in order to
sense biopolymer has been applied by Majumdar in Berkeley
University in the United States and Fritz in an IBM Swiss Zurich
research center. And a method to sense protein and gene using a
biological reaction on a surface of a micro cantilever is published
in the Nature Biotechnology 19, 856-860 (2001) and Science 288,
316-318 (200).
[0005] The sensing method by measuring the static deflection can be
realized by focusing light source (e.g. laser) on the surface of
the cantilever and collecting a position sensitive diode. In this
case, there is a limit of difficulty to form a small-sized system
because the sensing method requires a constant temperature device
to minimize a motion of the microcantilever caused by an external
heat and an optical space to estimate a deflection precisely.
[0006] There is another sensing method using a change of a resonant
frequency. Thundat et al. of Oak Ridge national lab reveals in
Applied Physics Letters 80, 2219-2221 (2002) that spring constant
is changed when Na+ ion is adsorbed onto a surface of the
microcantilever from measuring a resonant frequency. Some
researchers including those in IBM Swiss Zurich research center
have reported that a specific gas in the air can be sensed by
measuring a resonant frequency thereof. However, in these cases, an
additional actuator separate from the cantilever is required to
attain the resonance and this causes a problem that the size of a
chamber (i.e., a space required for a surface reaction with a
sample to be sensed by the microcantilever) is inevitably
increased, so that it becomes difficult to implement a diagnosis
chip or an analyzing unit reacting with the small amount of in the
range between a few pico liter and scores of micro liter.
[0007] Meanwhile, Microarrays, the conventional chips for the
detection of biopolymer such as DNA or protein, have been suggested
that the formation of several gold arrays on a substrate such as
silicon wafer in order to form an organic molecular film thereon
recognizing bio-bodies, and perform a surface modification, and
interacts the target biopolymer. After interaction, the interacted
biopolymer is scanned by laser, and then, fluorescent light is
emitted owing to an attached fluorescent substance. The fluorescent
light can be detected by using an optical sensing device (or
detector). This method also has demerits in needs of bulky light
source and the detector and labeling process, thereby making it
difficult to obtain a compact size.
SUMMARY OF THE INVENTION
[0008] An advantage of the present invention is a detection system
for detecting a small amount of protein related to disease using
piezoelectric monolithic cantilever system by resonant frequency
shift even in a liquid as well as in the air.
[0009] These and other advantages of the invention are accomplished
by a sample apparatus and a method for detecting and measuring a
small amount of biopolymer such as DNA, protein, enzyme or a cell.
To achieve these and other advantages and in accordance with the
purpose of the present invention, as embodied and broadly described
herein, there is provided a biopolymer detection system using a
cantilever comprising: an infinitesimal fluid transfer system
including an inlet for allowing a reactant to be injected
therethrough, and an infinitesimal introduction channel for
connecting the inlet and a reaction chamber; and a cantilever
sensor embedded in the reaction chamber and including a cantilever
with one end fixed at a substrate, a piezoelectric thin film for
self-actuating and sensing deposited on at least one side of an
upper surface and a lower surface of the cantilever, a lower
electrode formed at a lower surface of the piezoelectric film and
an upper electrode formed at an upper surface of the piezoelectric
film, an electric pad for supplying electric current to both the
lower electrode and the upper electrode, and a molecular
recognition layer formed at least one upper surface of the
cantilever and the driving film so as to react to an analysis
material.
[0010] To achieve the above advantage, there is also provided a
method for fabricating a biopolymer detection system using a
cantilever, comprising: a step of forming a cantilever sensor
including a cantilever by using a MEMS technique, forming a
actuating capacitor by deposition of piezoelectric film at a
surface of the cantilever and de upper and lower electrodes at
upper and lower surfaces of the piezoelectric film, deposition of
an electronic pad at certain portions of the upper electrode and
the lower electrode, and forming a molecular recognition layer on
at least one side of the cantilever and the actuating capacitor; a
step of forming upper and lower molds to form an inlet, a reaction
chamber and an infinitesimal introduction channel for connecting
the inlet with the reaction chamber; a step of putting a dissolved
mold material in the molds and solidifying the mold material to
form upper and lower plates; a step of fixing the cantilever sensor
in the reaction chamber; and a step of bonding the upper and lower
plates.
[0011] The foregoing and other advantages, features and aspects of
the present invention will become more apparent from the following
detailed description of the present invention when taken in
conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The accompanying drawings, which are included to provide a
further understanding of the invention and are incorporated in and
constitute a part of this specification, illustrate embodiments of
the invention and together with the description serve to explain
the principles of the invention.
[0013] In the drawings:
[0014] FIGS. 1 to 3 illustrate structures of one embodiment of the
present invention, in which:
[0015] FIG. 1 is a projective perspective view of an element
detecting system using a cantilever in accordance with one
embodiment of the present invention;
[0016] FIG. 2 is a perspective view of a cantilever sensor of FIG.
1; and
[0017] FIG. 3 is a sectional view taken along lines III-III of FIG.
2;
[0018] FIGS. 4 and 5 illustrate a result of sensing a microelement
in the air, in which:
[0019] FIG. 4 is a graph showing a resonant frequency in the air;
and
[0020] FIG. 5 is a graph showing a quantitative analysis result of
CRP (C Reactive Protein) in the air by using a method for detecting
micro element in accordance with one embodiment of the present
invention; and
[0021] FIGS. 6 to 8 are graphs showing an analysis result in a
liquid by a cantilever type of the element detecting system with a
cantilever.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENT
[0022] Reference will now be made in detail to the preferred
embodiments of the present invention, examples of which are
illustrated in the accompanying drawings.
[0023] FIGS. 1 to 3 illustrate structures of one embodiment of the
present invention, in which: FIG. 1 is a projective perspective
view of an element detecting system using a cantilever in
accordance with one embodiment of the present invention, FIG. 2 is
a perspective view of a cantilever sensor of FIG. 1, and FIG. 3 is
a sectional view taken along lines III-III of FIG. 2.
[0024] As shown in these drawings, the present invention provides
an element detecting system comprising an infinitesimal fluid
transfer system 100, and a cantilever sensor 200 fixed in a
reaction chamber 115 of the infinitesimal fluid transfer system
100.
[0025] The infinitesimal fluid transfer system 100 is formed by
combining an upper plate 110 with lower plate 120. The upper plate
110 includes inlets 111a and 111b, an outlet 117 formed penetrating
the upper plate 110, a mixing chamber 113 and the reaction chamber
115 formed insertedly and non-penetratingly at the surface of the
upper plate 110 facing the lower plate, and inlet channel channels
112a, 112b and 114 and an inlet channel 116 formed insertedly at
the surface of the upper plate 110 facing the lower plate 120.
[0026] The inlet channels 112a, 112b and 114 include entrance
channels 112a and 112b connecting the inlets 111a and 111b and the
mixing chamber 113, and a mixing channel 114 connecting the mixing
chamber 113 with the reaction chamber 115. The outlet channel 116
connects the reaction chamber 115 with the outlet 117.
[0027] The mixing channel 114 is connected to a lower end of the
reaction chamber 115 (i.e. end near the lower plate 120), and the
outlet channel 116 is connected to an upper end of the reaction
chamber 115.
[0028] In the embodiment of the present invention shows that all
the channels and the chambers are formed at the upper plate 110,
but the invention includes that they are formed at the lower plate
120 or at both sides of the upper and lower plates 110 and 120.
[0029] The upper plate 110 and the lower plate 120 can be made of a
polymer material (e.g. PDMS (Polydimethyl Siloxane),
polycarbonate), or a glass material (e.g. Pyrex, quartz).
[0030] The cantilever sensor 200 includes a cantilever 220 with one
end fixed at a substrate 210, a driving film 230 stacked at an
upper surface of the cantilever 220; an insulation film formed to
cover electric pads 241 and 242 for supplying electricity to the
driving film 230, an electric signal pad (not shown) for detecting
an electric signal, and the driving film 230 to prevent occurrence
of conduction in a liquid, and a molecular recognition layer 260
formed at a lower surface of the cantilever 220 to react to an
analysis material.
[0031] The cantilever 220 is formed as a triple layer consisting of
a silicon oxide film 221, a silicon nitride film 222 stacked on the
silicon oxide film 221 and a silicon oxide film 223 stacked on the
silicon nitride film 222. In this case, the cantilever 220 is not
necessarily formed as the triple layer but formed as a double layer
of the silicon oxide film or silicon nitride film and silicon or
formed as a single layer of silicon or silicon nitride film.
[0032] The driving film 230 includes a lower electrode 233 stacked
at an upper surface of the cantilever 220, a piezoelectric film 232
stacked on the lower electrode and an upper electrode 231 stacked
at an upper surface of the piezoelectric film 232.
[0033] The insulation film 250 is made of an inorganic material
such as SiOx by using a PECVD (Plasma Enhanced Chemical Vapor
Deposition), APCVD (Atmospheric Pressure Chemical Vapor Deposition)
or evaporation device, or formed by evaporating a film made of an
organic material such as parylene. An upper electrode opening 241
and a lower electrode opening 242 are formed to connect the
electric pad 240 and the upper electrode 231 and lower electrode
233.
[0034] The electric pads includes an upper electric pad 241
connected to the upper electrode 231 and a lower electric pad 242
connected to the lower electrode 233. The electric pads are also
connected to both the upper electrode 231 and the lower electrode
233. The electric pads are to detect a resonant frequency as an
electric signal, and an optically transparent window is formed in
the infinitesimal fluid transfer system in order to optically
detect the electric signal.
[0035] The molecular recognition layer 250 is formed by fixing a
reacting material to a measurement-subject material after modifying
a self assembled monolayer (SAM) at the lower surface of the
cantilever 220 or fixing a reacting material to the
measurement-subject material after depositing Cr and Au at the
lower surface of the cantilever 220 and modifying a calixcrown SAM
thereon. For example, a material such as prostate specific antibody
can be fixed on the SAM. However, without being restricted thereto,
various materials can be fixed on the SAM according to the kind of
a measurement-subject material.
[0036] As shown in FIG. 2, in the cantilever sensor, more than two
cantilevers 220 are formed on one substrate 210, and the driving
film, the insulation film 250, the electrode pad 240, the electric
signal pad (not shown) and the molecular recognition layer 260 are
formed on each cantilever 220. In this respect, in order to obtain
a reference resonant frequency, the molecular recognition layer 260
may not be formed on some cantilever 220.
[0037] A method for fabricating the element detecting system using
a cantilever constructed as described above, includes a step of
forming a cantilever sensor by using a MEMS technique; a step of
forming upper and lower plates of the infinitesimal fluid transfer
system; and a step of fixing the upper and lower plates and the
cantilever sensor.
[0038] In the step of forming the cantilever sensor, the driving
film, the electrode pad and the molecular recognition layer are
formed by repeating deposition and etching on the substrate by
using the MEMS technique.
[0039] In the step of forming the upper and lower plates, after
molds are formed, which forms the inlets 111a and 111b, the outlet
117, the channels 112a, 112b, 114 and 116, the mixing chamber 113
and the reaction chamber 115, a dissolved mold material is put in
the molds and solidified to form the upper and lower plates.
[0040] In the step of fixing the upper and lower plates and the
cantilever sensor, the cantilever sensor 200, as formed in the step
of forming the cantilever sensor, is fixed to the reaction chamber
115 in the following manner: The substrate 210 is fixed between the
upper plate 110 and the lower plate 120 such that the cantilever
lever 220 can be protruded in the reaction chamber 115, and then,
the upper plate 110 and the lower plate 120 are bonded, wherein the
preferable mold material is a PDMS, and the mold is preferably made
of die steel, Teflon or silicon.
[0041] The element detecting using the cantilever in accordance
with the present invention operates as follows.
[0042] When different reactants are injected to the inlets 111a and
111b, these reactants are mixed while passing the mixing chamber
113 and the mixing channel 114 through the inlet channels 112a and
112b. As the mixture is filled up to the upper portion of the
reaction chamber 115 through the mixing channel 114, it passes the
outlet channel 116 and externally discharged through the outlet
117.
[0043] Meanwhile, a specific material of the mixture filled in the
reaction chamber 115 is fixed at the molecular recognition layer
260 of the cantilever sensor 200. Thereafter, when electricity is
supplied to electric pads 251 and 252 while changing a frequency,
the piezoelectric film 232 is bent vertically, and at this time, a
resonant frequency of the cantilever 220 is sensed through the
electric signal pad.
[0044] Thereafter, it is possible to obtain a small amount of
biopolymer fixed at the molecular recognition layer 260 by
comparing the sensed resonant frequency with resonant frequency
measured when the reaction material is not fixed to the molecular
recognition layer 260.
[0045] The element detecting system using a cantilever in
accordance with the present invention has the following
advantages.
[0046] Firstly, thanks to the driving film formed as the
piezoelectric film, an actuator device is not additionally
required, and thus, an overall size of the system is considerably
reduced.
[0047] Secondly, by coupling the element detecting system to an
infinitesimal transfer system, a desired reaction material can be
sensed easily by using a very small amount of sample whose scale is
from a few nano liters up to scores of micro liter.
[0048] Thirdly, since the resonant frequency is sensed by the
electric pad, an additional optical space is not required. In this
respect, however, the modification of the present invention
proposes a method for measuring the resonant frequency by forming
an optically transparent window.
[0049] Moreover, by forming several cantilevers on one substrate
210, one cantilever is used for frequency measurement and the
others are used for measuring a sensing frequency. Thus, it is
possible to reduce not only an error occurrence probability due to
several recognitions, but also the number of obtaining resonant
frequency. In addition, the molecular recognition layer is made of
a different material in each cantilever 220, so that several
materials can be detected at one time.
[0050] The method for detecting a microelement with the element
detecting system using a cantilever is described below.
[0051] First, a method for detecting a small amount of biopolymer
in a solution includes: a first step of injecting a cleaning
solution such as a PBS solution into the inlets 111a and 111b to
fill the reaction chamber 115; a second step of supplying
electricity to the electric pads 251 and 252 to obtain a reference
resonant frequency of the cantilever; a third step of supplying an
analysis solution toward the inlets 111a and 111b and maintaining
the state so as for the analysis solution to react to the molecular
recognition layer 260; a fourth step of injecting a cleaning
solution into the inlets 111a and 111b to fill the chamber 115; a
fifth step of applying electricity to the electric pads 251 and 252
to obtain a resonant frequency of the cantilever; and a step of
comparing the reference resonant frequency obtained in the second
step with the resonant frequency obtained in the fifth step, in
order to analyze a specific material in the analysis solution.
[0052] FIGS. 6 to 8 are graphs showing an analysis result in a
liquid by using the element detecting system using a
cantilever.
[0053] FIG. 6 is a graph showing a result of the resonant frequency
obtained in the second step. Accordingly, it is noted that the
small amount of biopolymer detecting system using a cantilever in
accordance with the present invention can obtain a resonant
frequency even in a liquid.
[0054] FIG. 7 is a graph showing a result of detection of mass of
prostate cancer in a liquid by using PSA (Prostate Specific
Antibody) serum.
[0055] With reference to FIG. 7, after an analysis solution was
injected into the inlets 111a and 111b to fill the reaction
chamber, electricity was supplied to the electric pad at every
predetermined period to obtain a resonant frequency of the
cantilever. It's the result obtained from a patient of prostate
cancer having a 1 ng/ml PSA antigen density by diluting serum of
the patient. From the result, it was possible to analyze the PSA
having the density of 1 ng/ml, which shows that proteins in serum,
blood or blood plasma can be measured in the range of a few ng or
pg.
[0056] FIG. 8 shows a result of measurement of viscosity and
density of a fluid by using the element detecting system using a
cantilever in accordance with the present invention. It is noted
that a resonant frequency is being changed according to a change in
a content of water and glycerol, that is, viscosity and density of
a liquid. This result shows that it can be applied as a
blood-detecting sensor that can determine a degree of an illness
through detection of an electrical resonant signal according to a
fine change in viscosity of blood. Accordingly, by measuring
viscosity and density of serum or blood, decrease or increase of
red blood cells can be detected, according to which a degree of an
illness can be determined.
[0057] A method for detecting a micro material in the air includes:
a first step of injecting a cleaning solution into the inlets 11a
and 111b to fill the chamber 115; a second step of injecting
nitrogen gas into the inlets 111a and 111b to remove the cleaning
solution from the chamber 115; a third step of supplying
electricity to the electric pads 251 and 252 to obtain a reference
resonant frequency of the cantilever; a fourth step of supplying an
analysis solution toward the inlets 111a and 111b and maintaining
the state for a predetermined time so as for the analysis solution
to react to the molecular recognition layer 260; a fifth step of
injecting a cleaning solution into the inlets 111a and 111b to fill
the chamber 115; a sixth step of injecting nitrogen gas into the
inlets 111a and 111b to remove the cleaning solution from the
chamber 115; a seventh step of applying electricity to the electric
pads 251 and 252 to obtain a resonant frequency of the cantilever;
and a step of comparing the reference resonant frequency obtained
in the third step with the resonant frequency obtained in the
seventh step.
[0058] The cleaning solution is preferably a PBS.
[0059] FIGS. 4 and 5 illustrate results of detecting a small amount
of protein related to disease in the air. Specifically, FIG. 4
illustrates a profile of the resonant frequency in the air, and
FIG. 5 illustrates a quantitative analysis result of CRP (C
Reactive Protein) in the air by using the method for detecting a
small mount of protein in accordance with the present
invention.
[0060] As mentioned above, in the present invention, the resonant
frequency can be measured even in a liquid as well as in the air,
the element detecting system can be used as a sensor for detecting
a biopolymer, as a humidity sensor by forming the molecular
recognition layer with gelatin, as a mercury detecting sensor, as a
high sensitive gas sensor, and as a weight sensor that is able to
detect a weight from a few pico grams to a few micro grams.
[0061] Meanwhile, for the purpose of detecting a biopolymer such as
protein or DNA, an antibody is formed on the molecular recognition
layer, and then, in order not to change characteristics of the
biopolymer such as protein or DNA, a temperature is not changed at
a room temperature and only a pressure is lowered to gasificate the
biopolymer, the detection subject, so that it can react to the
molecular recognition layer.
[0062] As so far described, the present invention has various
advantages as follows. In this respect, the present invention is
considered established even when the following effects are not
exerted.
[0063] That is, for example, first, by providing the cantilever
using the piezoelectric film, vibration of a constant frequency can
be applied to the cantilever without using an additional actuator.
Thus, the size of the cantilever sensor can be considerably reduced
and coupled to a fine fluid transfer system to measure a very small
amount of reaction material.
[0064] In addition, by having the insulation film, a resonant
frequency can be obtained even in a liquid, and a resonant
frequency that is changed over time in the liquid can be
obtained.
[0065] As the present invention may be embodied in several forms
without departing from the spirit or essential characteristics
thereof, it should also be understood that the above-described
embodiments are not limited by any of the details of the foregoing
description, unless otherwise specified, but rather should be
construed broadly within its spirit and scope as defined in the
appended claims, and therefore all changes and modifications that
fall within the metes and bounds of the claims, or equivalence of
such metes and bounds are therefore intended to be embraced by the
appended claims.
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